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Administrative data

Description of key information

Acute oral toxicity
LD50(female rats)=3129 mg/kg bw
Acute dermal toxicity
Conduct of an acute dermal toxicity study for cobalt bis(2-ethylhexanoate) is unjustified since dermal uptake is considered negligible (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).
Acute inhalation toxicity
According to section 2, annex XI of regulation (EC) 1907/2006, the conduct of an acute toxicity study via inhalation for cobalt bis(2-ethylhexanoate) is omitted. The substance is a waxy solid which is not capable in creating an inhalable atmosphere, thus testing is technically not feasible.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-11-17 to 2010-12-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Ace Animals, Inc., Boyertown, PA- Age at study initiation: 9 - 12 weeks- Weight at study initiation: 158 - 211 g- Fasting period before study: Naive rats were fasted overnight.- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 1996). Litter paper was placed beneath the cage and was changed at least three times per week.- Diet: Purina Rodent Chow # 5012; feed was replaced approx. three hours after final dosing.- Water (ad libitum): Filtered tap water- Acclimation period: 6-28 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 16-23- Relative humidity (%): 17-65; humidity was below the targeted lower limit for 13 days during the study. A portable humidifier was used to increase the humidity levels during this time.- Air changes (per hr): 14- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
other: Carboxymethylcellulose (CMC) in distilled water.
Details on oral exposure:
VEHICLE- Concentration in vehicle: The test substance was administered as a 30% w/w mixture in 0.5% w/w solution of CMC in distilled water.- Justification for choice of vehicle: Preliminary solubility testing conducted by EPSL, indicated that the test material was insoluble in distilled water and corn oil, and mixtures in 0.5%CMC in excess of 30% (i.e., 40-80%) were too viscous to be administered properly.MAXIMUM DOSE VOLUME APPLIED:5,000 mg/kgDOSAGE:Individual doses were calculated based on the initial body weights, taking into account the specific gravity (determined by EPSL) and concentration of the test mixture. Due to high volume of test suspension to be administered (27.64 mL/kg) to the 5,000 mg/kg dose group, each animal´s dose was equally divided into two portions and administered approx. two hours apart.Initially, a single animal received a limit dose of 5,000 mg/kg. Due to the mortality of this animal, the Main test was conducted. Using the default starting level of 175 mg/kg and following the Up and Down procedure, eight additional females were dosed.
Doses:
175, 550, 1,750 or 5,000 mg/kg
No. of animals per sex per dose:
1 animal per 175 mg/kg dose level1 animal per 550 mg/kg dose level3 animals per 1,750 mg/kg dose level3 animals per 5,000 mg/kg dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Individual body weights were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing or after death. The animals were observed for mortality, signs of gross toxicity and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing or until death occurred. - Necropsy of survivors performed: yes; surviving rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all decedents and euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.- Other examinations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhea and coma.
Statistics:
The Acute Oral Toxicity (Guideline 425) Statistical Program (Westat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.
Sex:
female
Dose descriptor:
LD50
Effect level:
3 129 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 750 - <= 5 000
Mortality:
All animals of the 175, 550, 1750 mg/kg dose levels survived the test substance administration.All animals of the 5000 mg/kg dose level died within five days of test substance administration.
Clinical signs:
All animals of the 175, 550, 1750 mg/kg dose levels appeared active and healthy during the study; no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were noted.Toxic signs noted in the decedents of the 5000 mg/kg dose level group prior to death included nasal and mouth discharge, irregular respiration, hypoactivity, hunched posture, ano-genital staining, soft feces, diarrhea and/or reduced fecal volume.
Body weight:
All animals of the 175, 550, 1750 mg/kg dose levels gained body weight.
Gross pathology:
For all animals of the 175, 550, 1750 mg/kg dose levels no gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-days observation period.Gross necropsy of the decedents of the 5000 mg/kg dose level group revealed moderatly red to extremely discolouration of the lungs and/or liver, and distention of the intestines and/or stomach.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 of cobalt 2-ethylhexanoate is estimated to be 3,129 mg/kg of body weight in female rats with an approx. 95% confidence interval of 1,750 mg/kg (lower) to 5,000 mg/kg (upper).According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 129 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
Weight of evidence information

Justification for classification or non-classification

Acute oral toxicity

The reference Lowe (2011) is considered as the key study for acute oral toxicity and will be used for classification. Female Sprague-Dawley rats were dosed at 175, 550, 1750 or 5000 mg/kg orally via gavage.

During the conduct of the study mortalities occurred at the highest dose group

LD50 oral, rat = 3,129 mg/kg bw

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2,000 mg/kg body-weight, hence no classification is required.

 

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

 

Acute dermal toxicity

Conduct of an acute dermal toxicity study for cobalt bis(2-ethylhexanoate) is unjustified since dermal uptake is considered negligible (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

 

Specific target organ toxicant (STOT) – single exposure: dermal

Conduct of an acute dermal toxicity study for cobalt bis(2-ethylhexanoate) is unjustified since dermal uptake is considered negligible (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

 

Acute inhalation toxicity

According to section 2, annex XI of regulation (EC) 1907/2006, the conduct of an acute toxicity study via inhalation for cobalt bis(2-ethylhexanoate) is omitted. The substance is a waxy solid which is not capable in creating an inhalable atmosphere, thus testing is technically not feasible.

 

Specific target organ toxicant (STOT) – single exposure: inhalation

According to section 2, annex XI of regulation (EC) 1907/2006, the conduct of an acute toxicity study via inhalation for cobalt bis(2-ethylhexanoate) is omitted. The substance is a waxy solid which is not capable in creating an inhalable atmosphere, thus testing is technically not feasible.